Medical Innovations From France

Medical Innovations from France

BY BETHANY ATHERTON, CONTRIBUTING EDITOR

Target Cancer, Diabetes, Cardiovascular Disease

SOUTH OF FRANCE. I AM ON MY way to Marseille with my friend Reine. Out the window, there is a wintry landscape with a low-lying mist winding through the grape vines and the Florentine cypress trees. As we drift south through a countryside of limestone cliffs, we are suddenly faced with a panorama of sea meeting sky; a sea
whipped to steely blue and an azure sky swept clean by the brutal Mistral, the wind from Siberia. These are colors that make Provence famous, the palette artists have endeavored to translate to canvas for centuries. We are on the Autoroute du Soleil, the freeway that connects Paris with the Mediterranean. Momentarily distracted, the scenery poignantly belies the true nature of our outing. We have an appointment
at 9:20 a.m. at the Institut Paoli-Calmettes where Reine will have her last session of chemotherapy for ovarian cancer.

Our driver makes good time despite the craziness of French drivers late for work and the labyrinth of Marseille streets dating from the Middle Ages. Transportation, bon de transport, is one of the benefits of socialized medicine. Patients with chronic conditions undergoing treatment will be conveyed to their appointments by an authorized chauffeur.

We arrive at Paoli-Calmettes, or “the factory,” as Reine dubs it and I soon see why. In a residential area, the stark white Bauhaus-like factory stands out against a background of old stone walls, blue shutters and burntorange roof tiles. The automatic doors
open with a pneumatic whoosh and Reine walks up to a post where she inserts her patient card. It spits out everything she will need for the day: appointment times, doctors’ names and even the list of medications she will be administered during the
chemotherapy session. Everything goes like clockwork and, after a meeting with a nurse and a doctor, we go into a “box,” a room with five medical reclining chairs, where Reine is hooked up to her IV solution bags. Gradually, the room fills with other patients and I grasp how it resembles a factory assembly line.

In the fight against cancer, Institut Paoli-Calmettes ranks third after the school of cancer research, Gustave Roussy, and Institut Curie, both in Paris. My contact, Elisabeth Belarbi, explains that the ratings fluctuate. Sometimes Institut Paoli-Calmettes (IPC) and Curie swap places due in part to IPC’s emphasis on Therapeutic Patient Education (TPE). A shortage of doctors in France just under 20 years ago led the medical society to focus on the concept of encouraging the patient to become more proactive with his chronic illness and its treatment. TPE allows patients to improve their knowledge and skills not only concerning their illness, but also their treatment. The greatest
challenge faced by TPE is encouraging a patient to accept behavior change.

According to Francois Bourdillon, president of the French Society of Public Health, “Motivational interviewing and cognitive-behavioral approaches contribute greatly here and allow both the preparation and support of patients during progressive step-by-step change.”

The efficiency of TPE has been substantiated. It is a humanistic medical approach wherein patients become active participants in their own treatment with the objective of improving their quality of life, as well as reducing complications. Results indicate that
behavioral techniques and physical exercise improve psychosocial functioning and health-related quality of life (HRQoL) in cancer patients and survivors. In the case of diabetic patients, amputations have decreased 80 percent over 10 years and 50 percent maintenance of weight loss over five years has been observed.

Additionally, Institut Paoli-Calmettes is unique in that its research and patient care take place at the same address. “If we want to advance our knowledge in the field of oncology, it is imperative that research be tied to the care of our patients,” explains IPC Scientific Director Jean-Paul Borg.

IPC research is determined first and foremost by the needs of the oncologist and his patient and the manner in which the patient responds to treatment. When a patient proves resistant to treatment, for example, the researcher can swiftly examine the biological peculiarities of the tumor to identify a potential biomarker associated with
the resistance.

At the Institut Curie—named after Marie Curie, two-time Nobel Prize winner whose work led to the discovery of radium and its therapeutic properties—Interleukin-2 (IL-2) has become the star. IL-2, a molecule in the immune system constellation, is a cytokine. Cytokines are small proteins (such as interferon) released by certain cells in the

immune system. They aid cell-to-cell communication in moments of immune response and stimulate cell movement toward trauma, inflammation and infection. Immunologist Eliane Piaggio has been studying IL-2 for several years. In trial phase, the cytokine is administered in high doses to boost the immune system and to act on cancer cells. Given the toxicity of this therapeutic approach, it has not been used to date.

“The objective of our research project is to use the IL-2 complex to direct the immuneresponse against certain cancers,” explains Piaggio.

Institut Curie will be the first to open an immunotherapy center for cancer in France where Piaggio and her team will continue to tackle IL-2 therapy in clinical trials.

Recently, Piaggio received funding from the French National Research Agency which will enable her to further her research, as well, on the efficacy of IL-2 on type I diabetes. From animal models, she has observed that approximately 30 percent of subjects with
type I diabetes develop anti-IL-2 auto-antibodies, thus their immune system destroys the insulin-producing beta cells in the pancreas.

“They (autoantibodies) can be detected before the onset of diabetes symptoms and could be used as diagnostic biomarkers,” explains Piaggio.

In 2011, a group of diabetologists in Grenoble, France, sponsored by the Center for Studies and Research for the Intensification of Diabetes Treatment, launched an artificial pancreas project in order to improve type I diabetes patients’ quality of life and their regulation of glycemia. The result was Diabeloop, the artificial pancreas comprised
of a continuous glucose sensor, a smartphone-like terminal and an insulin delivering pump worn by the patient. The completely automated process eliminates the patient’s need to prick his finger multiple times per day. Should the test trials be successful, Diabeloop, currently being tested in 10 French hospitals, will be available in 2018.

Institut Curie is synonymous, literally and figuratively, with cutting-edge medical research. After burning his arm with radium salts, Pierre Curie and his wife, Marie Curie, mentioned the possibility that radium could be used in the treatment of cancer. Fast-forward to today and imagine a nurse intrigued by the odor of wounds caused by breast cancer; imagine a dog trainer specializing in the detection of explosives. Put them together and you have an Institut Curie team training two dogs to smell cancer. Project
Kdog employs Thor and Nykios and their trainers, Isabelle Fromantin and Jacky Experton. After only six months of research, the dogs have demonstrated
an astonishing talent: from 130 swatches soaked with sweat, the duo was able to
identify, with 100 percent efficiency, the 79 swatches furnished by women diagnosed
with breast cancer.

The tests carried out at Magnac-Laval in southwest central France present the dogs with the small samples of cloth in sterile dishes. Stage two will be to repeat the experiment with two new dogs of different breeds, trained by someone else.

“The next trial will involve 1,000 volunteer women,” says Experton.

Using dogs to detect cancer provides women with a non-invasive alternative and is certainly cheaper than mammography machinery. If the trials, anticipated to be completed by 2020, are successful, women could post their sample cloths to wherever detector dogs are located.

While the clinical trials are focused on breast cancer, Institut Curie envisages continuing the trials for other hard-to-detect tumors such as ovarian cancer.

In assessing the paradigm linking cancer, diabetes, cardiovascular disease (CD) and the presence, all too often, of obesity, French researchers and doctors have begun to advocate the catchphrase, “To start thinking on your own is already part of the solution.”
Toxicologist André Cicolella, president of the French Environmental Health Network,

discusses “the invisible scandal,” the presence of endocrine disruptors, pesticides, chemical molecules of all kinds present in consumer goods, pharmaceuticals, food, drinking water, and the air we breathe. CD is the second leading cause of death in France. However, according to Professor Jean-Pierre Bassand, M.D., professor of Cardiology at the University of Besançon
Franche-Comté, cardiovascular diseases, particularly atherosclerotic disease hardening and narrowing of the arteries), are the leading cause of premature death and permanent disability in France.

CDs have increased at an astonishing rate in recent years and while poor diet and physical inactivity are major factors, these lifestyle changes alone fail to fully account for the magnitude and rapidity of the epidemic. Attention is being turned toward other possible causes, such as environmental endocrine disrupting chemicals (EDC). Emerging preliminary evidence implicates multiple pollutants in the development of atherosclerosis and CD.

Mice, commonly used as models of macrovascular disease, treated with tetrachlorodibenzo-p-dioxin (TCDD, also known as Agent Orange, the well known
pesticide used in the Vietnam War), demonstrated early onset and greater severity of atherosclerotic lesions. Similar results were attained using simple air pollution.

“Health depends on the quality of man’s relation to his ecosystem,” explains Cicolella. “To combat these chronic diseases, one must take responsibility for the environment. Combatting these diseases is everyone’s business.”

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